The present invention relates to a composition of matter comprising particles which contain choline chloride to be administered in a rumen-protected and post-ruminally effective form, in particular to a ruminant.
It has become common practice to supplement the diet of animals with certain feed additives, the use of which may either generally improve the health conditions of the animals, or increase feed efficiencies in meat producing animals, or increase milk productivity and/or milk quality in milk producing animals.
Among these additives, special attention has been recently dedicated to choline, with particular reference to the breeding of ruminants.
The term “ruminant” means an even-toed hoofed animal which has a complex of 3- or 4-chambered stomach and which is characterized by chewing again what it has already swallowed (e.g.: cattle, bison, sheep, goats and the like).
Unless otherwise stated, the term “choline” generally means choline itself, choline derivatives, a choline containing composition, a choline compound or a mixture of choline compounds. Choline is available in many forms, such as: choline, choline chloride, choline bitartrate, choline dihydrogen citrate, choline bicarbonate, choline sulphate and choline hydroxide, among other derivatives. Any choline form in principle has been considered applicable in the art, because in general choline itself, and not the form it is in, is the effective additive.
The preferred form of choline is generally choline chloride, because it is readily available and has a high specific content of choline.
Choline is an essential nutrient for normal animal growth and performance. Choline is an essential component for cell walls, nerve transmission (it is a precursor of acetyl-choline), fat metabolism and transport. Choline is also an important source of labile methyl groups (labile methyl groups which, in the diet of animals, may also be supplied by methionine and betaine and may also be synthesised using folic acid and vitamin B12).
Normally, choline is provided in adequate quantities to ruminants as a result of synthesis by ruminal microflora, e.g. in cow-feeding programs using primarily forage based diets. Protozoa appear to be the primary species involved in the synthesis of choline. Consequently, diets that result in ruminal conditions which compromise growth and proliferation of protozoa may result in inadequate choline supply to the animal and may benefit from addition of choline to the diet. Examples of these types of diets may be: high-concentrate diets, which frequently produce ruminal pH in the range of 5.5 to 5.8, which is less than optimal for proliferation of protozoa; diets providing for the inclusion of fats, which fats may induce a further reduction of the protozoan populations, probably either as a consequence of lower ruminal pH that occurs with fat feeding or as a direct effect of fats on protozoa.
Supplemental choline seems to have an effect on feed efficiencies.
Furthermore, as a lipotropic compound and a methyl donor, researchers have shown that supplemental dietary choline has an effect both on milk yield and composition. This effect has been found in ruminants and, in particular, in dairy cows.
Choline also seems to improve conveying the mobilised lipids from adipose tissues through the liver to the mammary gland.
In general choline is beneficial to the health conditions of the animals: supplemental choline may prevent “low-fat” syndrome, particularly when feeding ration of low forage:concentrate ratio.
The choline-methionine relationship appears to be critical. In periods of negative energy balance during the life of the animal, the interaction between the metabolism of methyl groups, methionine and glucose can affect methionine requirements. In the case of choline deficiencies, methionine seems to replace choline. When the methionine is at an insufficient level, the choline spares the methionine as a methyl donor. This fact suggests the possibility of supplementing choline to reduce catabolism of methionine as a methyl donor, thus probably affecting a metabolic saving of this amino acid which is essential for protein synthesis.
Incorporation of choline therefore is an important factor in supplementing the diet of ruminants. At the same time, it is recognized that choline, as many biologically active materials, when employed as a feed additive directly mixed in the ration, is inefficiently utilized by ruminants due to degradation thereof in the rumen, which is essentially a continuous fermenter. A ruminant allows a great variety of micro-organisms to live in its rumen under neutral conditions (i.e. at pHs ranging from 5 to 8) and makes advantageously use of their microbial action to digest and use ingredients (such as cellulose) which cannot inherently be digested by a mono-gastric animal and have no direct nutritive value for the host, converting them into products which can be assimilated and utilized by the host. On the other hand, the microbial action occurring in the rumen presents certain disadvantages. Very valuable substances (such as choline) may be subjected to either chemical change or digestion by the rumen micro organisms and transformed into substances of much lower nutritive value.
Therefore, choline must be supplied orally to ruminants in a rumen-protected form.
The term “ruminally protected” (or “rumen protected”) means having the capability of passing through the rumen without being substantially decomposed.
It is critical that the choline be “post-ruminally effective”, which means orally administered choline which passes through the rumen but does not take effect until it has reached a point past the rumen. Therefore, the rumen-protected form of choline must be capable to let choline be delivered in the abomasum and/or in its subsequent digestive tract, for efficient breeding of ruminants.
The most common technique used to produce rumen-protected choline is to encapsulate it in a protective matrix which shields choline from ruminal environment, but allows its release in the post-ruminal tract of the digestive system. The protective matrix may or may not comprise an outer, continuous coating which physically protects a core containing the active substance.
Encapsulation may be obtained by the well known fluidised-bed technology. It allows particles to be freely flowing from each other, atomising the coating material in fine droplets, which will touch the particles in movement and spread over the surface. The thin film layers of molten coating material crystallize in an air stream at a temperature lower than the melting point of the coating material. Such parameters as pressure, flow-rate and temperatures are used to optimise the process. The use of such technology is restricted to the encapsulation of compounds in solid state.
Encapsulation can furthermore be obtained by putting powdered materials to be encapsulated in a rotating device. This makes the powdered materials rotate in a helical motion along the periphery of the rotating device. At the same time a suitable binding solution is sprayed into the rotating device. The impact due to the centrifugal forces and the permanent rolling motion of the material to be encapsulated alongside the polished interior walls of the rotating device together with the binding solution produces the capsules/microcapsules.
Other technologies consist of spraying a mixture of active substance and coating material at a temperature above the melting point into an air stream at a temperature below the melting point. Spraying said mixture through a nozzle with a small opening using sufficient air-pressure will result in the formation of micro-spheres containing core and coating material. U.S. Pat. No. 5,496,571 discloses an application of this technology to the encapsulation of choline chloride, consisting of spraying a mixture of a liquid phase of choline chloride with various lipids, which results in the formation of microspheres containing liquid choline chloride and coating material. U.S. Pat. No. 5,190,775 discloses a technology for encapsulating choline chloride according to which a liquid phase of choline chloride is absorbed by a cereal carrier before applying the coating material. The so obtained granules, constituted by cereal carriers with absorbed choline chloride, may then be suspended in the coating material, which has been previously brought to the liquid state, and the suspension sprayed into a “freezing chamber”. Alternatively the so obtained granules may be suspended into a flow of air and sprayed with the coating material.
Many patent documents report a number of formulations of the protective matrix which have been developed specifically for the rumen protection of numerous active substances and, in particular, for the rumen protection of choline. Given the conditions in the rumen, where the aggressive microflora lives in an aqueous environment with a pH ranging approximately from 5 to 7, most of the protective matrices developed in the art include some hydrophobic, water insoluble substance to prevent premature release of choline in the rumen, almost always mixed and combined with some hydrophilic substance to control release of choline in the post-rumen digestive tract. The protective matrices so obtained have been conceived so composed and structured as to disintegrate at acidic pH in the post ruminal tract.
As stated above, the preferred form of choline is generally choline chloride, because it is readily available and has a high specific content of choline. Choline chloride, as described above, is usually used in a liquid phase (usually in a water diluted form), either directly dispersed in the embedding matrix in the form of one or more droplets (as in U.S. Pat. No. 5,496,571), or absorbed by a cereal carrier which is, in turn, subsequently embedded in the protective matrix (as in U.S. Pat. No. 5,190,775).
In general, the extent of rumen protection offered to choline by the protective matrix may be expressed by the “rumen-by-pass quality” of the rumen protected form of choline. This “rumen-by-pass quality” (or, simply, either “rumen-by-pass” or “by-pass”) may be defined as the percentage of the amount of choline originally present in the core of the capsules which is still available in the post-rumen portion of the digestive intestinal tract of the ruminant after the passage through the rumen.
Further to the fact that the compositions developed in the prior art for the protective matrix and/or for the protective coating are generally complicated and need to be provided with a very finely tuned structure and/or texture in order to be effective, the characteristic drawback of the above mentioned, existing technologies for the encapsulation or microencapsulation of choline chloride (which, as above stated, is one of the most preferred forms of supplemental choline), is that degeneration of the rumen-by-pass quality of choline chloride occurs unless the capsules are immediately administered as such to the animal, without performing any other particular operation on them. This problem is partly already recognized in the art: U.S. Pat. No. 6,106,871, in particular, clearly states that in order to prevent degradation of the choline compound prior to use, it is preferable that the rumen-protected choline compound is not mixed with any other ingredient prior to mixing with the ration and that, furthermore, it is also preferable to mix the choline compound with the ration just prior to feeding the cow.
Degeneration of the rumen-by-pass quality may occur also in either or all of the following cases: when the micro-capsules are mixed in the feed premix or in the feed mix ultimately fed to the ruminants; when, in this mixed forms, the micro-capsules are stored for a certain period of time; when the micro-capsules are subjected to a pelleting process, by which the microcapsules containing choline chloride are included in feed pellets constituting either a single ingredient of, or the whole, feed ration of the animal; when the so obtained feed pellets are stored for a given period of time prior to administering them to the ruminants.
Furthermore the nature of the coating materials usually used does not resist to the harsh conditions (mechanical pressure, thermal stresses and temperatures applied) which they are subjected to during the process of making feed pellets. Pelleting, in particular, can be defined as the agglomeration of relatively small particles into larger particles (ranging from 3 mm to 5 cm or more) by means of a mechanical process in combination with moisture, heat and pressure. The typical temperatures applied range from 55° C. to 90° C.
If the protective matrix is either not effective or damaged, so that it may show some leakages, humidity in particular becomes a concern and the damage which may be induced by humidity if the microcapsule shows some leakages (together with the consequent dramatic reduction in rumen-by-pass quality which may so result) is well known in the art. This is particularly true for choline chloride.
None of the prior art solutions is able to solve the above mentioned problems, neither deals with the problem of stability of the encapsulated choline chloride against degeneration of rumen-by-pass quality when subjected to its preparation and mixing with other feed components. All the types of micro-capsules described in the art, which contain choline chloride, are either not capable to survive to the harsh conditions of the pelleting process, or are at least insufficient to provide a good protection against a strong degeneration of rumen-by-pass quality of their choline chloride content. This may be a big problem, stated that most of cattle feed supplements in Europe and in the United States are produced in pelleted form. In this process stress caused by high temperature, pressure and/or injected steam could worsen the mechanical damage that may occur during the mixing process that is preliminarily carried out.